Core Insights - Tenaya Therapeutics reported positive interim data from the MyPEAK-1 clinical trial for TN-201, indicating a favorable safety profile and improvements in hypertrophy and NYHA classification [1][4] - The RIDGE study highlighted a significant disease burden among adults with PKP2-associated ARVC, emphasizing the unmet need for effective treatments [1][8] - The company has extended its cash runway into the second half of 2026, supported by recent funding and cost containment measures [1][9] Clinical Programs - **TN-201**: - Interim data from the MyPEAK-1 trial showed TN-201 was well tolerated at a dose of 3E13 vg/kg, with robust DNA transduction and RNA expression [4] - All three patients in the initial cohort achieved NYHA Class I post-treatment, with two showing improvements in hypertrophy measures [4] - Initial data from Cohort 2 is expected in the second half of 2025 [4] - **TN-401**: - Enrollment for the RIDGE-1 trial is on track, with initial data anticipated in the second half of 2025 [8] - The RIDGE study revealed over 80% of participants experienced significant arrhythmias, indicating a high unmet need for TN-401 [8] Financial Highlights - For Q1 2025, Tenaya reported a net loss of $26.9 million, or $0.24 per share, an improvement from a net loss of $32.2 million, or $0.40 per share in Q1 2024 [9][14] - Research and development expenses decreased to $21.1 million from $25.1 million year-over-year [7][14] - Cash, cash equivalents, and marketable securities totaled $88.2 million as of March 31, 2025, with additional net proceeds of approximately $48.8 million from a public offering [7][16] Business Updates - The company implemented a restructuring plan to focus financial resources on clinical execution, which is expected to significantly reduce cash expenses [8][9] - Tenaya received an $8.0 million clinical grant from the California Institute for Regenerative Medicine to support the TN-401 trial [8]

Core Insights - Tenaya Therapeutics announced interim data from the RIDGE study, the largest natural history study of adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) due to PKP2 gene mutations, highlighting the high burden of arrhythmias and severe disease progression despite standard treatments [1][3][4] Group 1: Study Overview - The RIDGE study has enrolled over 175 patients across approximately 20 clinical sites in the U.S., UK, France, Germany, Italy, and Sweden, focusing on clinical characteristics and medical history of PKP2-associated ARVC patients [3][4] - Interim data from 144 adults with PKP2-associated ARVC were analyzed as of February 2025 [3] Group 2: Key Findings - 83% of participants with Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, indicating a higher risk of life-threatening ventricular arrhythmias [4] - 49% of participants with available Holter monitoring data had a history of ventricular tachycardia [4] - 60% of patients with MRI data showed disease progression, as indicated by measures of right and left ventricular function and heart tissue health [4] - Electrocardiogram results indicated that a majority of patients had T-wave inversions, suggesting ventricular strain or myocardial injury [4][5] Group 3: Treatment Insights - Current treatment approaches, including medications and surgical interventions, have proven insufficient in addressing the high burden of arrhythmias and disease progression in PKP2-associated ARVC patients [3][4] - Tenaya is developing TN-401 gene therapy, which aims to deliver a functional PKP2 gene to heart muscle cells using an adeno-associated virus serotype 9 (AAV9) [2][10] Group 4: Future Directions - Enrollment is ongoing for Tenaya's Phase 1b clinical trial, RIDGE-1, to assess the safety, tolerability, and activity of a one-time dose of TN-401, with initial safety and biopsy data expected in the second half of 2025 [6][11] - The RIDGE study is expected to serve as a control arm for assessing the efficacy of TN-401 gene therapy in PKP2-associated ARVC [7]

Core Insights - Tenaya Therapeutics announced promising interim data from the MyPEAK-1 Phase 1b/2 clinical trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), presented at the 2025 American College of Cardiology Scientific Sessions [1][2][3] Group 1: Clinical Trial Data - TN-201 was well tolerated at a dose of 3E13 vg/kg, with treatment-emergent adverse events primarily mild and manageable [2][3] - All three patients in Cohort 1, who had severe disease at baseline, achieved NYHA Class I, indicating no limitations on physical activity [3] - Serial biopsies showed sustained presence of TN-201 DNA in the heart and robust RNA expression, increasing up to 13-fold from Week 8 to Week 52 post-dose [2][3] - MyBP-C protein levels increased from 56% to 59% and from 62% to 64% of normal between Week 8 and Week 52 for Patients 1 and 2, respectively [2][3] - Cardiac troponin levels decreased by more than 60% in two patients, returning to normal or near normal [2][3] Group 2: Future Expectations - Enrollment for Cohort 2 is expected to be completed in the first half of 2025, with initial data to be reported in the second half of 2025 [1][2][7] - The company anticipates sharing additional data from Cohort 1 and initial safety and biopsy data from Cohort 2 later this year [3][7] - Tenaya has updated its cash guidance into the second half of 2026, positioning itself to achieve important clinical data milestones for both TN-201 and TN-401 gene therapy programs [3] Group 3: Disease Context - MYBPC3-associated HCM is a severe condition affecting approximately 120,000 patients in the U.S., with no approved therapeutics addressing its underlying genetic cause [11][12] - Patients with MYBPC3 mutations are at higher risk for serious complications, including heart failure and sudden cardiac death, particularly if diagnosed before age 40 [10][11]

Core Insights - Tenaya Therapeutics announced promising interim data from the MyPEAK-1 Phase 1b/2 clinical trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), presented at the 2025 American College of Cardiology Scientific Sessions [1][2][3] Group 1: Clinical Trial Data - TN-201 was well tolerated at a dose of 3E13 vg/kg, with treatment-emergent adverse events primarily mild and manageable [2][3] - All three patients in Cohort 1, who had severe disease at baseline, achieved NYHA Class I, indicating no limitations on physical activity [3][4] - Serial biopsies showed sustained presence of TN-201 DNA in the heart and robust RNA expression, increasing up to 13-fold from Week 8 to Week 52 post-dose [2][3] - MyBP-C protein levels increased from 56% to 59% and from 62% to 64% of normal between Week 8 and Week 52 for Patients 1 and 2, respectively [2][3] - Cardiac troponin levels decreased by more than 60% in two patients, returning to normal or near normal [2][3] Group 2: Future Expectations - Enrollment for Cohort 2 is expected to be completed in the first half of 2025, with initial data to be reported in the second half of 2025 [1][2][8] - The company anticipates sharing additional data from Cohort 1 and initial safety and biopsy data from Cohort 2 later this year [3][8] - Tenaya has updated its cash guidance into the second half of 2026, positioning itself to achieve important clinical data milestones for both TN-201 and TN-401 gene therapy programs [3][4] Group 3: Background on MYBPC3-Associated HCM - MYBPC3 mutations are the most common genetic cause of HCM, affecting approximately 120,000 patients in the U.S. alone [12][13] - Patients with MYBPC3-associated HCM are at higher risk for serious outcomes, including heart failure and sudden cardiac death, with younger patients experiencing more rapid disease progression [11][12]

Core Insights - Tenaya Therapeutics has published positive preclinical data for its gene therapy candidate TN-201, aimed at treating MYBPC3-associated hypertrophic cardiomyopathy (HCM) [1][2][3] Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][13] - The company is currently evaluating TN-201 in the MyPEAK-1 Phase 1b/2 clinical trial, which is designed to assess the safety and efficacy of the therapy [11] Preclinical Findings - TN-201, an AAV9-based gene therapy, has shown dose-dependent increases in MyBP-C protein levels, improving cardiac function in preclinical models [2][5] - Treatment with TN-201 reversed left ventricular hypertrophy, a key feature of HCM, demonstrating significant improvements in cardiac parameters [2][8] - The therapy achieved near-maximal efficacy at doses of 3x10 vg/kg, with durable effects lasting up to 20 months post-treatment [9][15] Clinical Development - The MyPEAK-1 trial is enrolling symptomatic adults diagnosed with MYBPC3-associated HCM, testing doses of 3E13 vg/kg and 6E13 vg/kg [11] - Initial findings from the first cohort of patients in the MyPEAK-1 trial are expected to be presented at the upcoming American College of Cardiology Scientific Sessions [4] Disease Context - MYBPC3 mutations are the most common genetic cause of HCM, affecting approximately 120,000 patients in the U.S. [10] - The condition leads to severe symptoms and high rates of serious outcomes, with no approved therapies targeting the underlying genetic cause [10]

Core Insights - Tenaya Therapeutics is set to present new clinical and disease burden data related to its MYBPC3-associated hypertrophic cardiomyopathy (HCM) program at the American College of Cardiology's Annual Scientific Session from March 29-31, 2025 [1][2] Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on discovering, developing, and delivering potentially curative therapies for heart disease [5] - The company is advancing a pipeline that includes TN-201, a gene therapy for MYBPC3-associated HCM, TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), and TN-301, a small molecule HDAC6 inhibitor for heart failure with preserved ejection fraction (HFpEF) [5] Clinical Trials and Presentations - Data from the MyPEAK-1 Phase 1b/2 clinical trial will be presented, featuring one-year assessments of the first two patients who received TN-201 gene therapy, along with baseline biopsy and six-month assessments from a third patient [2] - A poster presentation will discuss findings from the Sarcomeric Human Cardiomyopathy Registry (SHaRe), highlighting differences in disease burden among adults with HCM caused by MYBPC3 mutations [3] Event Details - The presentations will take place on March 30 and March 31, 2025, at the ACC conference, with specific sessions dedicated to heart failure and cardiomyopathies [6]

Core Insights - Tenaya Therapeutics is set to present new clinical and disease burden data related to its MYBPC3-associated hypertrophic cardiomyopathy (HCM) program at the American College of Cardiology's Annual Scientific Session from March 29-31, 2025 [1][2] Group 1: Clinical Developments - The company is advancing TN-201, an AAV9-based gene therapy targeting MYBPC3-associated HCM, which is caused by insufficient levels of myosin-binding protein C (MyBP-C) [2][5] - Data from the MyPEAK-1 Phase 1b/2 clinical trial will be presented, including one-year assessments of the first two patients and six-month assessments from a third patient in the 3E13 vg/kg cohort [2][3] Group 2: Research Findings - A poster presentation will discuss findings from the Sarcomeric Human Cardiomyopathy Registry (SHaRe), highlighting differences in disease burden among adults with HCM due to MYBPC3 mutations [3][6] - The presentations will be made by notable experts, including Dr. Milind Desai from the Cleveland Clinic [2][6] Group 3: Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease, with a pipeline that includes TN-201, TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy, and TN-301, a small molecule HDAC6 inhibitor for heart failure with preserved ejection fraction [5]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM___________TO___________ Commission File Number 001-40656 TENAYA THERAPEUTICS, INC. (Exact name of Registrant as specified in its Charter) (State or other jurisdict ...

Exhibit 99.1 Tenaya Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update Dosing Initiated in Cohort 2 of the MyPEAK™-1 Phase 1b/2 Clinical Trial of TN-201 for Treatment of MYBPC3-Associated Hypertrophic Cardiomyopathy TN-201 – Gene Therapy for MYBPC3-Associated Hypertrophic Cardiomyopathy • In December 2024, Tenaya reported promising early data from the first cohort of patients in the MyPEAK-1 Phase 1b/2 clinical trial of TN-201 gene therapy. o Preliminary da ...

Core Insights - Tenaya Therapeutics has initiated dosing in Cohort 2 of the MyPEAK-1 Phase 1b/2 clinical trial for TN-201, targeting MYBPC3-associated hypertrophic cardiomyopathy (HCM) [1][4] - The company reported promising early data from Cohort 1 of the MyPEAK-1 trial, with TN-201 showing good tolerability and evidence of transgene expression [4][3] - Financial results for Q4 and full year 2024 indicate a net loss of $111.1 million, with cash reserves expected to support operations into mid-2026 following a recent financing round [10][11][8] Clinical Development Updates - The MyPEAK-1 trial is designed to assess the safety and efficacy of TN-201 in patients with HCM due to MYBPC3 mutations, with data from Cohort 1 accepted for presentation at the American College of Cardiology meeting [4][3] - Initial data from the RIDGE-1 Phase 1b trial for TN-401, targeting PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), is expected in the second half of 2025 [1][9] - The company plans to release data from its pediatric study, MyClimb, in the second half of 2025, which aims to characterize disease burden in MYBPC3 patients diagnosed before age 18 [4] Financial Performance - For Q4 2024, Tenaya reported R&D expenses of $18.7 million, down from $22.9 million in Q4 2023, while G&A expenses decreased to $6.0 million from $8.6 million [10][11] - The company’s cash position as of December 31, 2024, was $61.4 million, a decrease from $104.6 million in 2023, but bolstered by a recent public offering that raised approximately $48.9 million [10][18] - The net loss for Q4 2024 was $23.8 million, or $0.28 per share, compared to a net loss of $29.9 million, or $0.40 per share, in Q4 2023 [11][16]